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Biomedicines
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Head and Neck Tumors, 3rd Edition
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Head and Neck Tumors, 3rd Edition

A special issue of Biomedicines (ISSN 2227-9059). This special issue belongs to the section "Cancer Biology and Oncology".

Deadline for manuscript submissions: 31 August 2024 | Viewed by 7841

Special Issue Editors

Dr. Silvia Di Agostino

E-Mail Website
Guest Editor
IRCCS Regina Elena National Cancer Institute, Roma, Italy
Interests: genomic instability; cell cycle checkpoints; dna repair; transcriptional regulation; molecular oncology; head and neck; p53 family; mutant p53; hippo pathway
Special Issues, Collections and Topics in MDPI journals
Prof. Dr. Jan B. Vermorken

E-Mail Website
Guest Editor
1. Center for Oncological Research Antwerp, University of Antwerp, Universiteitsplein 1, 2610 Wilrijk, Belgium
2. Department of Oncology, Antwerp University Hospital, Wilrijkstraat 10, 2650 Edegem, Belgium
Interests: cancer biology; cancer therapy; oncology; toxicity; pharmacodynamics; chemotherapy; treatment; cancer; tumors; pharmacokinetics
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

In the last 5 to 10 years, a wide range of information about head and neck cancers, both malignant and benign, has been published, bringing about key prognostic and therapeutic improvements for patients. Recently, a more complex approach has been used for making therapeutic decisions, including otorhinolaryngological treatments and skull-base surgery. However, the identification of more precise and reliable prognostic markers is necessary to make adequate therapeutic decisions.

This Special Issue aims to present original, translational, or clinical research and review articles that focus on the different aspects of head and neck cancer treatment, including the mechanisms of disease, translational medical research, biomaterials, biological therapies and immunotherapies, biomarkers, treatment of recurrent and metastatic disease, and the personalization of treatment based on the molecular characteristics of individual tumors.

Dr. Silvia Di Agostino
Prof. Dr. Jan B. Vermorken
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Biomedicines is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2600 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • head and neck tumors
  • microenvironment
  • predictive markers
  • therapy

Published Papers (9 papers)

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Research

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11 pages, 842 KiB  
Article
Efficacy of Office-Based Salivary Ductal Steroid Irrigation for Managing Post-Irradiation Xerostomia in Head and Neck Cancer Patients: A Retrospective Study
by Yen-Chun Chen, Nguyen-Kieu Viet-Nhi, Luong Huu Dang, Chin-Hui Su and Shih-Han Hung
Biomedicines 2024, 12(5), 1033; https://doi.org/10.3390/biomedicines12051033 - 8 May 2024
Viewed by 146
Abstract
Post-irradiation xerostomia remains a significant quality of life concern for patients with head and neck cancers. Conventional therapies offer limited effectiveness. This study aims to investigate the therapeutic potential of office-based salivary ductal steroid irrigation in patients with post-irradiation xerostomia. This single-center observational [...] Read more.
Post-irradiation xerostomia remains a significant quality of life concern for patients with head and neck cancers. Conventional therapies offer limited effectiveness. This study aims to investigate the therapeutic potential of office-based salivary ductal steroid irrigation in patients with post-irradiation xerostomia. This single-center observational study recruited 147 head and neck cancer patients suffering from post-irradiation xerostomia between November 2020 and October 2022. All included subjects received at least one round of successful salivary ductal cannulation and irrigation. The primary measure of efficacy was improvement in subjective xerostomia and objective salivary amylase levels. A logistic regression was employed to evaluate factors affecting treatment responsiveness. The response rate among nasopharyngeal cancer (NPC) patients was 74.8%, and that among non-NPC cancer was 65.6%, without significant intergroup differences. The statistical analysis revealed no significant influence of age, gender, or disease stage on treatment responsiveness. Post-treatment salivary amylase levels were significantly higher in responsive non-NPC patients. In conclusion, salivary ductal steroid irrigation emerged as a promising therapeutic modality for the management of post-irradiation xerostomia in head and neck cancer patients. While no explicit factors were predictive of responsiveness, the high rate of symptom improvement suggests that this therapy may be a viable alternative for patients that are refractory to standard treatments. Full article
(This article belongs to the Special Issue Head and Neck Tumors, 3rd Edition)
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11 pages, 258 KiB  
Article
Global DNA Methylation Level in Tumour and Margin Samples in Relation to Human Papilloma Virus and Epstein–Barr Virus in Patients with Oropharyngeal and Oral Squamous Cell Carcinomas
by Jadwiga Gaździcka, Krzysztof Biernacki, Karolina Gołąbek, Katarzyna Miśkiewicz-Orczyk, Natalia Zięba, Maciej Misiołek and Joanna Katarzyna Strzelczyk
Biomedicines 2024, 12(4), 914; https://doi.org/10.3390/biomedicines12040914 - 20 Apr 2024
Viewed by 396
Abstract
Background: Aberrant DNA methylation is a common epigenetic modification in cancers, including oropharyngeal squamous cell carcinoma (OPSCC) and oral squamous cell carcinoma (OSCC). Therefore, the analysis of methylation levels appears necessary to improve cancer therapy and prognosis. Methods: The enzyme-linked immunosorbent assay (ELISA) [...] Read more.
Background: Aberrant DNA methylation is a common epigenetic modification in cancers, including oropharyngeal squamous cell carcinoma (OPSCC) and oral squamous cell carcinoma (OSCC). Therefore, the analysis of methylation levels appears necessary to improve cancer therapy and prognosis. Methods: The enzyme-linked immunosorbent assay (ELISA) was used to analyse global DNA methylation levels in OPSCC and OSCC tumours and the margin samples after DNA isolation. HPV detection was conducted by hybridisation using GenoFlow HPV Array Test Kits (DiagCor Bioscience Inc., Hong Kong, China). EBV detection was performed using real-time PCR with an EBV PCR Kit (EBV/ISEX/100, GeneProof, Brno, Czech Republic). Results: OPSCC tumour samples obtained from women showed lower global DNA methylation levels than those from men (1.3% vs. 3.5%, p = 0.049). The margin samples from OPSCC patients with HPV and EBV coinfection showed global DNA methylation lower than those without coinfection (p = 0.042). G3 tumours from OSCC patients had significantly lower levels of global DNA methylation than G2 tumours (0.98% ± 0.74% vs. 3.77% ± 4.97%, p = 0.010). Additionally, tumours from HPV-positive OSCC patients had significantly lower global DNA methylation levels than those from HPV-negative patients (p = 0.013). In the margin samples, we observed a significant negative correlation between global DNA methylation and the N stage of OSCC patients (rS = −0.33, p = 0.039). HPV-positive OPSCC patients had higher global DNA methylation levels than HPV-positive OSCC patients (p = 0.015). Conclusion: We confirmed that methylation could be changed in relation to viral factors, such as HPV and EBV, as well as clinical and demographical parameters. Full article
(This article belongs to the Special Issue Head and Neck Tumors, 3rd Edition)
14 pages, 1252 KiB  
Article
Friend or Foe? Exploring the Role of Cytomegalovirus (HCMV) Infection in Head and Neck Tumors
by Aleksandar Trivic, Jovica Milovanovic, Djurdjina Kablar, Ana Tomic, Miljan Folic, Ana Jotic, Nada Tomanovic, Ana Marija Tomic, Igor Djoric and Marko Jankovic
Biomedicines 2024, 12(4), 872; https://doi.org/10.3390/biomedicines12040872 - 15 Apr 2024
Viewed by 643
Abstract
Although not regarded as an oncogenic pathogen, the human cytomegalovirus (HCMV) has been associated with a wide array of malignancies. Conversely, a number of studies report on possible anti-tumor properties of the virus, apparently mediated via HCMV-galvanized T-cell tumor killing; these were recently [...] Read more.
Although not regarded as an oncogenic pathogen, the human cytomegalovirus (HCMV) has been associated with a wide array of malignancies. Conversely, a number of studies report on possible anti-tumor properties of the virus, apparently mediated via HCMV-galvanized T-cell tumor killing; these were recently being investigated in clinical trials for the purposes of anti-cancer treatment by means of dendritic cell vaccines and HCMV-specific cytotoxic T cells. In the present study, we have analyzed the relation between a complement of head-and-neck tumors and HCMV infection across 73 countries worldwide using Spearman correlation, univariate and multivariate regression analysis. Intriguingly, HCMV was found to be pro-oncogenic in patients with nasopharyngeal carcinoma; contrarywise, the virus manifested an inverse (i.e., anti-tumor) association with the tumors of the lip/oral region and the salivary glands. Although this putative protective effect was noted initially for thyroid neoplasia and hypopharyngeal tumors as well, after multivariate regression analysis the connection did not hold. There was no association between laryngeal cancer and HCMV infection. It would appear that, depending on the tissue, HCMV may exert both protective and oncogenic effects. The globally observed protective feature of the virus could potentially be utilized in future therapeutic approaches for salivary tumors and neoplasia in the lip/oral region. As correlation does not necessarily imply causation, more in-depth molecular analyses from comprehensive clinical studies are warranted to substantiate our findings. Full article
(This article belongs to the Special Issue Head and Neck Tumors, 3rd Edition)
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21 pages, 1539 KiB  
Article
Exploring the Link between Inflammatory Biomarkers and Head and Neck Cancer: Understanding the Impact of Smoking as a Cancer-Predisposing Factor
by Jarosław Nuszkiewicz, Joanna Wróblewska, Marlena Budek, Jolanta Czuczejko, Alina Woźniak, Marta Maruszak-Parda and Karolina Szewczyk-Golec
Biomedicines 2024, 12(4), 748; https://doi.org/10.3390/biomedicines12040748 - 27 Mar 2024
Viewed by 687
Abstract
Head and neck cancer (HNC) is associated with significant morbidity globally, with smoking recognized as a key risk factor. This study investigates the interplay between smoking and inflammatory biomarkers in HNC development. The study involved 50 HNC patients, divided into smoking and non-smoking [...] Read more.
Head and neck cancer (HNC) is associated with significant morbidity globally, with smoking recognized as a key risk factor. This study investigates the interplay between smoking and inflammatory biomarkers in HNC development. The study involved 50 HNC patients, divided into smoking and non-smoking groups, and a control group of 30 healthy individuals. Serum levels of 48 cytokines, chemokines, growth factors, and other inflammatory markers were meticulously assessed. Significant differences in the levels of an extensive panel of inflammatory markers were observed between the patient groups and healthy controls. Elevated macrophage colony-stimulating factor (M-CSF) in both HNC groups implicated increased activity in pathways known for immunomodulation, proliferation, and angiogenesis during HNC cancerogenesis. In contrast, non-smokers with HNC demonstrated higher levels of interleukin 10 (IL-10) and interleukin 15 (IL-15), suggesting a more robust immune response. Platelet-derived growth factor BB (PDGF-BB) levels were particularly high in smokers with HNC. Smoking seems to alter the levels of crucial biomarkers in HNC, potentially affecting disease progression and responses to treatment. The data indicate that smokers may experience a more aggressive cancer phenotype, while non-smokers maintain a profile suggestive of a more active and effective immune response against HNC. Full article
(This article belongs to the Special Issue Head and Neck Tumors, 3rd Edition)
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17 pages, 5258 KiB  
Article
Gene-Expression Patterns of Tumor and Peritumor Tissues of Smoking and Non-Smoking HPV-Negative Patients with Head and Neck Squamous Cell Carcinoma
by Anna Soboleva, Irina Arutyunyan, Enar Jumaniyazova, Polina Vishnyakova, Daria Zarubina, Eldar Nimatov, Andrey Elchaninov and Timur Fatkhudinov
Biomedicines 2024, 12(3), 696; https://doi.org/10.3390/biomedicines12030696 - 21 Mar 2024
Viewed by 768
Abstract
We studied the gene-expression patterns in specimens of tumor and peritumor tissue biopsies of 26 patients with head and neck carcinomas depending on smoking status. Histological and immunohistochemical examinations verified that all tumors belonged to the “classical” subgroup of head and neck carcinomas, [...] Read more.
We studied the gene-expression patterns in specimens of tumor and peritumor tissue biopsies of 26 patients with head and neck carcinomas depending on smoking status. Histological and immunohistochemical examinations verified that all tumors belonged to the “classical” subgroup of head and neck carcinomas, and the HPV-negative tumor status was confirmed. The expression of 28 tumor-associated genes determined by RT-PCR was independent of patients’ sex or age, TNM status, degree of differentiation, or tissue localization. Moreover, in peritumor tissue, none of the 28 genes were differentially expressed between the groups of smoking and nonsmoking patients. During oncotransformation in both studied groups, there were similar processes typical for HNSCC progression: the expression levels of paired keratins 4 and 13 were reduced, while the expression levels of keratin 17 and CD44 were significantly increased. However, further investigation revealed some distinctive features: the expression of the genes EGFR and TP63 increased significantly only in the nonsmoking group, and the expression of IL6, CDKN2A, EGF, and PITX1 genes changed only in the smoking group. In addition, correlation analysis identified several clusters within which genes displayed correlations in their expression levels. The largest group included 10 genes: TIMP1, TIMP2, WEE1, YAP, HIF1A, PI3KCA, UTP14A, APIP, PTEN, and SLC26A6. The genetic signatures associated with smoking habits that we have found may serve as a prerequisite for the development of diagnostic panels/tests predicting responses to different therapeutic strategies for HNSCC. Full article
(This article belongs to the Special Issue Head and Neck Tumors, 3rd Edition)
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17 pages, 3963 KiB  
Article
Genetic Mutations Associated with Inflammatory Response Caused by HPV Integration in Oropharyngeal Squamous Cell Carcinoma
by Mai Atique, Isis Muniz, Fatemeh Farshadi, Michael Hier, Alex Mlynarek, Marco Macarella, Mariana Maschietto, Belinda Nicolau, Moulay A. Alaoui-Jamali and Sabrina Daniela da Silva
Biomedicines 2024, 12(1), 24; https://doi.org/10.3390/biomedicines12010024 (registering DOI) - 21 Dec 2023
Cited by 1 | Viewed by 1393
Abstract
(1) Background: Head and neck cancer (HNC) ranks as the sixth most prevalent cancer in the world. In addition to the traditional risk factors such as alcohol and tobacco consumption, the implication of the human papillomavirus (HPV) is becoming increasingly significant, particularly in [...] Read more.
(1) Background: Head and neck cancer (HNC) ranks as the sixth most prevalent cancer in the world. In addition to the traditional risk factors such as alcohol and tobacco consumption, the implication of the human papillomavirus (HPV) is becoming increasingly significant, particularly in oropharyngeal cancer (OPC). (2) Methods: This study is based on a review analysis of different articles and repositories investigating the mutation profile of HPV-related OPC and its impact on patient outcomes. (3) Results: By compiling data from 38 datasets involving 8311 patients from 12 countries, we identified 330 genes that were further analyzed. These genes were enriched for regulation of the inflammatory response (RB1, JAK2, FANCA, CYLD, SYK, ABCC1, SYK, BCL6, CEBPA, SRC, BAP1, FOXP1, FGR, BCR, LRRK2, RICTOR, IGF1, and ATM), among other biological processes. Hierarchical cluster analysis showed the most relevant biological processes were linked with the regulation of mast cell cytokine production, neutrophil activation and degranulation, and leukocyte activation (FDR < 0.001; p-value < 0.05), suggesting that neutrophils may be involved in the development and progression of HPV-related OPC. (4) Conclusions: The neutrophil infiltration and HPV status emerge as a potential prognostic factor for OPC. HPV-infected HNC cells could potentially lead to a decrease in neutrophil infiltration. By gaining a better molecular understanding of HPV-mediated neutrophil immunosuppression activity, it is possible to identify a meaningful target to boost antitumor immune response in HNC and hence to improve the survival of patients with HNC. Full article
(This article belongs to the Special Issue Head and Neck Tumors, 3rd Edition)
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11 pages, 995 KiB  
Article
Immunohistochemical Assessment of Microvessel Density in OSCC: Spatial Heterogeneity of Angiogenesis and Its Impact on Survival
by Andreas Mamilos, Alexander Lein, Lina Winter, Markus Haas, Torsten E. Reichert, Tobias Ettl, Julian Künzel, Gerrit Spanier and Christoph Brochhausen
Biomedicines 2023, 11(10), 2724; https://doi.org/10.3390/biomedicines11102724 - 8 Oct 2023
Cited by 1 | Viewed by 915
Abstract
(1) Background Oral squamous cell carcinomas (OSCC) are a common malignancy of the oral cavity and are often diagnosed when they have already spread to the regional lymph nodes. Advanced stages of cancer are characterized by the development of distant metastases. Angiogenesis, a [...] Read more.
(1) Background Oral squamous cell carcinomas (OSCC) are a common malignancy of the oral cavity and are often diagnosed when they have already spread to the regional lymph nodes. Advanced stages of cancer are characterized by the development of distant metastases. Angiogenesis, a hallmark of cancer, is known to contribute to cancer progression and metastasis. High microvessel density (MVD) has been linked to poor clinical outcomes in various types of cancer. (2) Methods: In this study, we aimed to investigate the spatial heterogeneity of blood vessels by comparing the tumor center and invasion front and to evaluate its prognostic value in OSCC. A total of 71 OSCC patient specimens were collected. The tissue was immunohistochemically stained using CD31 antibody to assess the MVD in the tumor center and the invasion front. Furthermore, the associations between the histopathological parameters, including MVD, disease-free survival (DFS), and overall survival (OS) were computed. (3) Results: In our study, we found a significantly higher presence of blood vessels at the invasion front of OSCCs compared to the tumor center. However, we did not observe any significant differences in MVD between different tumor stages. High intratumoral MVD was shown to be a positive prognostic factor for DFS (p = 0.047). (4) Conclusions: To the best of our knowledge, we were the first to analyze MVD as a prognostic factor by considering its spatial heterogeneity in OSCC. However, further studies are warranted to further elucidate the complexity of microvascular spatial heterogeneity and its influence on prognosis. Full article
(This article belongs to the Special Issue Head and Neck Tumors, 3rd Edition)
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Review

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18 pages, 744 KiB  
Review
Potential Immunohistochemical Biomarkers for Grading Oral Dysplasia: A Literature Review
by Jakub Zdrojewski, Monika Nowak, Kacper Nijakowski, Jakub Jankowski, Andrea Scribante, Simone Gallo, Maurizio Pascadopoli and Anna Surdacka
Biomedicines 2024, 12(3), 577; https://doi.org/10.3390/biomedicines12030577 - 5 Mar 2024
Viewed by 955
Abstract
Oral cancer is a prevalent global health issue, with significant morbidity and mortality rates. Despite available preventive measures, it remains one of the most common cancers, emphasising the need for improved diagnostic and prognostic tools. This review focuses on oral potentially malignant disorders [...] Read more.
Oral cancer is a prevalent global health issue, with significant morbidity and mortality rates. Despite available preventive measures, it remains one of the most common cancers, emphasising the need for improved diagnostic and prognostic tools. This review focuses on oral potentially malignant disorders (OPMDs), precursors to oral cancer, specifically emphasising oral epithelial dysplasia (OED). The World Health Organisation (WHO) provides a three-tier grading system for OED, and recent updates have expanded the criteria to enhance diagnostic precision. In the prognostic evaluation of OED, histological grading is presently regarded as the gold standard; however, its subjectivity and unreliability in anticipating malignant transformation or recurrence pose notable limitations. The primary objective is to investigate whether specific immunohistochemical biomarkers can enhance OED grading assessment according to the WHO classification. Biomarkers exhibit significant potential for comprehensive cancer risk evaluation, early detection, diagnosis, prognosis, and treatment optimisation. Technological advancements, including sequencing and nanotechnology, have expanded detection capabilities. Some analysed biomarkers are most frequently chosen, such as p53, Ki-67, cadherins/catenins, and other proteins used to differentiate OED grades. However, further research is needed to confirm these findings and discover new potential biomarkers for precise dysplasia grading and minimally invasive assessment of the risk of malignant transformation. Full article
(This article belongs to the Special Issue Head and Neck Tumors, 3rd Edition)
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22 pages, 2599 KiB  
Review
Role of Akt/Protein Kinase B in Cancer Metastasis
by Mohammad Islam, Sarah Jones and Ian Ellis
Biomedicines 2023, 11(11), 3001; https://doi.org/10.3390/biomedicines11113001 - 8 Nov 2023
Cited by 1 | Viewed by 1162
Abstract
Metastasis is a critical step in the process of carcinogenesis and a vast majority of cancer-related mortalities result from metastatic disease that is resistant to current therapies. Cell migration and invasion are the first steps of the metastasis process, which mainly occurs by [...] Read more.
Metastasis is a critical step in the process of carcinogenesis and a vast majority of cancer-related mortalities result from metastatic disease that is resistant to current therapies. Cell migration and invasion are the first steps of the metastasis process, which mainly occurs by two important biological mechanisms, i.e., cytoskeletal remodelling and epithelial to mesenchymal transition (EMT). Akt (also known as protein kinase B) is a central signalling molecule of the PI3K-Akt signalling pathway. Aberrant activation of this pathway has been identified in a wide range of cancers. Several studies have revealed that Akt actively engages with the migratory process in motile cells, including metastatic cancer cells. The downstream signalling mechanism of Akt in cell migration depends upon the tumour type, sites, and intracellular localisation of activated Akt. In this review, we focus on the role of Akt in the regulation of two events that control cell migration and invasion in various cancers including head and neck squamous cell carcinoma (HNSCC) and the status of PI3K-Akt pathway inhibitors in clinical trials in metastatic cancers. Full article
(This article belongs to the Special Issue Head and Neck Tumors, 3rd Edition)
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